Targeting cytokinesis bridge proteins to kill high-CIN type tumors  

作　　者：Bingteng Xie Xiaoling Liang Wei Yue Jihong Ma Xinyu Li Na Zhang Pan Wang Chang Liu Xiaomeng Shi Jie Qiao Peng Zou Mo Li 

机构地区：[1]Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China [2]National Clinical Research Center for Obstetrics and Gynecology(Peking University Third Hospital),Beijing 100191,China [3]Key Laboratory of Assisted Reproduction(Peking University),Ministry of Education,Beijing 100191,China [4]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology(Peking University Third Hospital),Beijing 100191,China [5]Department of Anesthesiology,Peking University Third Hospital,Beijing,China [6]State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Science,Peking University,Beijing 100191,China [7]College of Chemistry and Molecular Engineering,Peking-Tsinghua Center for Life Sciences,PKU-IDG/McGovern Institute for Brain Research,Peking University,Beijing 100871,China

出　　处：《Fundamental Research》2021年第6期752-766,共15页自然科学基础研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(NSFC)(Grants No.81672610,81521002,81871160)to ML,and by the“Clinic+X”program(to ML)of Peking University.

摘　　要：As a common feature of tumors,chromosomal instability(CIN)not only forces carcinomatous evolution,but also loads cancer cells with extra pressure through a robust imbalance of genome patterning that may be used for cancer treatment.Errors in cytokinesis increase CIN,so cytokinesis components are valuable targets for treating cancer.However,due to the short time span and confined space of cytokinesis bridges,profiling cytokinesis fac-tors is challenging.Taking advantage of engineered ascorbate peroxidase(APEX2),we established a cytokinesis bridge-APEX reaction in living cells.A total of 218 cytokinesis bridge proteins were identified with high relia-bility.Knockdown of cytokinesis bridge genes generated micronuclei that activate the cGAS-pathway and cause apoptosis in cancer cells bearing high CIN rather than low CIN.Thus,our study proposes a strategy for killing high-CIN tumors regardless of tumor type,and provides a proteome resource of cytokinetic bridges for future research.

关 键 词：Cytokinesis bridge proteome APEX2 High-CIN tumors Micronuclei cGAS 

分 类 号：R73[医药卫生—肿瘤]